POS0536 REFINING THE SEROLOGICAL SCORES OF THE ACR/EULAR 2010 RHEUMATOID ARTHRITIS CLASSIFICATION CRITERIA: AN INTERNATIONAL STUDY
Authors: L. Van Hoovels, B. Vander Cruyssen, D. Sieghart, C. Bonroy, E. Nagy, R. Pullerits, S. Čučnik, C. Dahle, I. Heijnen, L. Bernasconi, F. Benkhadra, L. Bogaert, S. Van Den Bremt, A. Vanliedekerke, G. Vanheule, J. Robbrecht, L. Studholme, W. Claudine, R. Müller, D. Kyburz, C. Sjowall, A. Kastbom, R. Jese, B. Jovancevic, E. V. Kiss, P. Jacques, G. Steiner, P. Verschueren, X. Bossuyt
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatoid factor (RF) and anti-cyclic citrullinated protein/peptide antibodies (ACPA) are included in the ACR/EULAR 2010 classification criteria for rheumatoid arthritis (RA)(1). Both markers are given the same weight in the criteria. Objectives As the performance characteristics differ significantly between RF and ACPA(2), we set out to refine the serological scores for RA classification. Methods Diagnostic samples from 398 RA patients and from 1073 diseased controls were evaluated with five RF assays (two RF IgM isotype-specific assays and three total RF assays) and five ACPA IgG assays from five different manufacturers. Results Firstly, we harmonized thresholds between manufacturers based on predefined specificity for low positive (at 92.5% specificity for RF and at 97.5% specificity ACPA) and high positive results (at 97.5% specificity RF and at 99.0% specificity for ACPA). Next, we determined likelihood ratios (LRs) for RF, ACPA, and combinations of both, for negative, low positive, and high positive results. The LR was higher for ACPA than for RF, for high positive results than for low positive results and for double positivity than for single positivity. Based on these data we refined the weights of serological scores for classification (Table 1). Table 1. Refined weights of serological scores for RA classification RF negative RF low positive RF high positive ACPA negative 0 1 1 ACPA low positive 2 3 3 ACPA high positive 3 4 4 Application of such refined serological weights significantly increased the area under the curve of receiver operating characteristics analysis to distinguish RA from controls, significantly reduced the serological scores in the controls as well as the number of RA misclassifications without affecting the diagnostic sensitivity. Besides, we showed that combining predefined specificity thresholds with the refined serological scoring, reduced manufacturer-dependent variability in RA classification impacting RA classification for controls from 18.0-29.0% by ACR/EULAR to 11.0-13.0% (significantly increasing specificity) and for RA patients from 67.8-74.0% to 67.6-71.5% (without significantly affecting sensitivity). Conclusion Serological weight factors for RA classification can be improved by taking into account the antibody type (RF versus ACPA), the antibody level, and single or combined positivity. References [1]Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham COr, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 2010; 69: 1580-8. [2]Bossuyt X. Anticitrullinated protein antibodies: taking into account antibody levels improves interpretation. Ann Rheum Dis 2017; 76: e33. Acknowledgements We thank all participating diagnostic companies for the in-kind support of assays, their technical training and the constructive discussions. Furthermore, we are very thankful to the laboratory technicians of all participating laboratories for their most appreciated assistance in the performance of the RF/ACPA analyses. Disclosure of Interests Lieve Van Hoovels Speakers bureau: Thermo Fisher, Consultant of: Thermo Fisher, Grant/research support from: Thermo Fisher, Bert Vander Cruyssen: None declared, Daniela Sieghart Speakers bureau: Thermo Fisher, Consultant of: Thermo Fisher, Carolien Bonroy: None declared, Eszter Nagy: None declared, Rille Pullerits: None declared, Saša Čučnik: None declared, Charlotte Dahle: None declared, Ingmar Heijnen Speakers bureau: Thermo Fisher, Luca Bernasconi Speakers bureau: Thermo Fisher, Farid Benkhadra: None declared, Laura Bogaert: None declared, Stefanie Van Den Bremt: None declared, Ann Vanliedekerke: None declared, Geert Vanheule: None declared, Johan Robbrecht: None declared, Lucy Studholme: None declared, Wirth Claudine: None declared, Rüdiger Müller: None declared, Diego Kyburz: None declared, Christopher Sjowall: None declared, Alf Kastbom: None declared, Rok Jese: None declared, Boja Jovancevic: None declared, Emese Virag Kiss: None declared, Peggy Jacques: None declared, Günter Steiner Speakers bureau: Thermo Fisher, Consultant of: Thermo Fisher, Patrick Verschueren: None declared, Xavier Bossuyt Speakers bureau: Thermo Fisher, Consultant of: Thermo Fisher.